登録情報 データベース : EMDB / ID : EMD-13656 ダウンロードとリンクタイトル Structure of double-stranded DNA-bound MCM2-7 DH complexed with Cdc7-Dbf4 in the presence of ATP (3D auto-refined map) マップデータC1 3D auto-refinement of MD-(ATP) bound to double-stranded DNA 詳細 試料複合体 : MCM2-7 double hexamer bound to double-stranded DNA and two copies of Cdc7-Dbf4複合体 : synthetic double-stranded DNADNA : synthetic double-stranded DNA複合体 : MCM2-7 double hexamer bound to two copies of Cdc7-Dbf4タンパク質・ペプチド : DNA replication licensing factor MCM2タンパク質・ペプチド : DNA replication licensing factor MCM3タンパク質・ペプチド : DNA replication licensing factor MCM4タンパク質・ペプチド : DNA replication licensing factor MCM5タンパク質・ペプチド : DNA replication licensing factor MCM6タンパク質・ペプチド : DNA replication licensing factor MCM7タンパク質・ペプチド : Cell division control protein 7タンパク質・ペプチド : DDK kinase regulatory subunit DBF4 残り4件を表示 表示を減らす 詳細 キーワード Helicase / Activation / Kinase / Phosphorylation / REPLICATION機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
positive regulation of spindle attachment to meiosis I kinetochore / positive regulation of meiotic DNA double-strand break formation involved in reciprocal meiotic recombination / positive regulation of DNA replication initiation / positive regulation of kinetochore assembly / positive regulation of meiotic DNA double-strand break formation / negative regulation of exit from mitosis / Dbf4-dependent protein kinase complex / positive regulation of protein localization to kinetochore / positive regulation of nuclear cell cycle DNA replication / positive regulation of meiosis I ... positive regulation of spindle attachment to meiosis I kinetochore / positive regulation of meiotic DNA double-strand break formation involved in reciprocal meiotic recombination / positive regulation of DNA replication initiation / positive regulation of kinetochore assembly / positive regulation of meiotic DNA double-strand break formation / negative regulation of exit from mitosis / Dbf4-dependent protein kinase complex / positive regulation of protein localization to kinetochore / positive regulation of nuclear cell cycle DNA replication / positive regulation of meiosis I / regulation of cell cycle phase transition / MCM core complex / Assembly of the pre-replicative complex / Switching of origins to a post-replicative state / MCM complex binding / mitotic DNA replication preinitiation complex assembly / nuclear DNA replication / premeiotic DNA replication / pre-replicative complex assembly involved in nuclear cell cycle DNA replication / mitotic DNA replication / Activation of the pre-replicative complex / CMG complex / nuclear pre-replicative complex / Activation of ATR in response to replication stress / protein-containing complex localization / DNA replication preinitiation complex / MCM complex / replication fork protection complex / mitotic DNA replication checkpoint signaling / double-strand break repair via break-induced replication / single-stranded DNA helicase activity / mitotic DNA replication initiation / regulation of DNA-templated DNA replication initiation / silent mating-type cassette heterochromatin formation / DNA strand elongation involved in DNA replication / nuclear replication fork / DNA replication origin binding / chromosome, centromeric region / DNA replication initiation / subtelomeric heterochromatin formation / protein serine/threonine kinase activator activity / helicase activity / chromosome segregation / transcription elongation by RNA polymerase II / heterochromatin formation / single-stranded DNA binding / DNA helicase / forked DNA-dependent helicase activity / single-stranded 3'-5' DNA helicase activity / four-way junction helicase activity / double-stranded DNA helicase activity / eukaryotic translation initiation factor 2alpha kinase activity / chromosome, telomeric region / 3-phosphoinositide-dependent protein kinase activity / DNA-dependent protein kinase activity / ribosomal protein S6 kinase activity / histone H3S10 kinase activity / histone H2AXS139 kinase activity / histone H3S28 kinase activity / histone H4S1 kinase activity / histone H2BS14 kinase activity / histone H3T3 kinase activity / histone H2AS121 kinase activity / Rho-dependent protein serine/threonine kinase activity / histone H2BS36 kinase activity / histone H3S57 kinase activity / histone H2AT120 kinase activity / AMP-activated protein kinase activity / histone H2AS1 kinase activity / histone H3T6 kinase activity / histone H3T11 kinase activity / histone H3T45 kinase activity / DNA replication / non-specific serine/threonine protein kinase / cell division / protein serine kinase activity / protein serine/threonine kinase activity / centrosome / DNA damage response / chromatin binding / chromatin / signal transduction / ATP hydrolysis activity / zinc ion binding / nucleoplasm / ATP binding / metal ion binding / identical protein binding / nucleus / cytoplasm 類似検索 - 分子機能 Regulatory subunit Dfp1/Him1, central region / : / Dfp1/Him1, central region / BRCT domain / Zinc finger, DBF-type / DBF-type zinc finger superfamily / : / DBF zinc finger / Zinc finger DBF4-type profile. / Zinc finger in DBF-like proteins ... Regulatory subunit Dfp1/Him1, central region / : / Dfp1/Him1, central region / BRCT domain / Zinc finger, DBF-type / DBF-type zinc finger superfamily / : / DBF zinc finger / Zinc finger DBF4-type profile. / Zinc finger in DBF-like proteins / : / MCM3 winged helix domain / MCM4, winged helix domain / : / MCM5, C-terminal domain / DNA replication licensing factor Mcm5 / MCM3-like, winged helix domain / DNA replication licensing factor Mcm3 / Mini-chromosome maintenance complex protein 4 / DNA replication licensing factor Mcm6 / DNA replication licensing factor Mcm7 / Mcm6, C-terminal winged-helix domain / MCM6 C-terminal winged-helix domain / DNA replication licensing factor Mcm2 / Mini-chromosome maintenance protein 2 / Mini-chromosome maintenance, conserved site / MCM family signature. / MCM N-terminal domain / MCM N-terminal domain / MCM OB domain / MCM OB domain / Mini-chromosome maintenance protein / MCM, AAA-lid domain / MCM P-loop domain / MCM AAA-lid domain / MCM family domain profile. / minichromosome maintenance proteins / MCM domain / BRCT domain superfamily / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Winged helix-like DNA-binding domain superfamily / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain / Nucleic acid-binding, OB-fold / ATPases associated with a variety of cellular activities / AAA+ ATPase domain / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性 Cell division control protein 7 / DNA replication licensing factor MCM3 / DNA replication licensing factor MCM2 / Minichromosome maintenance protein 5 / DNA replication licensing factor MCM4 / DDK kinase regulatory subunit DBF4 / DNA replication licensing factor MCM7 / DNA replication licensing factor MCM6 類似検索 - 構成要素生物種 synthetic construct (人工物) / Saccharomyces cerevisiae (パン酵母)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 9.1 Å 詳細 データ登録者Saleh A / Noguchi Y / Aramayo R / Ivanova ME / Speck C 資金援助 英国, 4件 詳細 詳細を隠すOrganization Grant number 国 Biotechnology and Biological Sciences Research Council (BBSRC) BB/T005378/1 英国 Wellcome Trust 107903/Z/15/Z 英国 Medical Research Council (MRC, United Kingdom) A652-5PY40 英国 Wellcome Trust 206175/Z/17/Z 英国
引用ジャーナル : Nat Commun / 年 : 2022タイトル : The structural basis of Cdc7-Dbf4 kinase dependent targeting and phosphorylation of the MCM2-7 double hexamer.著者 : Almutasem Saleh / Yasunori Noguchi / Ricardo Aramayo / Marina E Ivanova / Kathryn M Stevens / Alex Montoya / S Sunidhi / Nicolas Lopez Carranza / Marcin J Skwark / Christian Speck / 要旨 : The controlled assembly of replication forks is critical for genome stability. The Dbf4-dependent Cdc7 kinase (DDK) initiates replisome assembly by phosphorylating the MCM2-7 replicative helicase at ... The controlled assembly of replication forks is critical for genome stability. The Dbf4-dependent Cdc7 kinase (DDK) initiates replisome assembly by phosphorylating the MCM2-7 replicative helicase at the N-terminal tails of Mcm2, Mcm4 and Mcm6. At present, it remains poorly understood how DDK docks onto the helicase and how the kinase targets distal Mcm subunits for phosphorylation. Using cryo-electron microscopy and biochemical analysis we discovered that an interaction between the HBRCT domain of Dbf4 with Mcm2 serves as an anchoring point, which supports binding of DDK across the MCM2-7 double-hexamer interface and phosphorylation of Mcm4 on the opposite hexamer. Moreover, a rotation of DDK along its anchoring point allows phosphorylation of Mcm2 and Mcm6. In summary, our work provides fundamental insights into DDK structure, control and selective activation of the MCM2-7 helicase during DNA replication. Importantly, these insights can be exploited for development of novel DDK inhibitors. 履歴 登録 2021年9月28日 - ヘッダ(付随情報) 公開 2022年6月8日 - マップ公開 2022年6月8日 - 更新 2023年12月13日 - 現状 2023年12月13日 処理サイト : PDBe / 状態 : 公開
すべて表示 表示を減らす